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| Status |
Public on Nov 23, 2015 |
| Title |
Whole genome expression signature of SWCNT and MWCNT vs. asbestos subchronic exposures to human pleural mesothelial cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Malignant mesothelioma is one of the most aggressive forms of cancer known. Recent studies have shown that carbon nanotubes (CNTs) are biopersistent and induce mesothelioma in animals, but the underlying mechanisms are not known. Here, we investigate the effect of long-term exposure to CNTs on the aggressive behaviors of human pleural mesothelial cells, the primary cellular target of human lung mesothelioma. We show that sub-chronic exposure (4 month) to single- and multi-walled CNTs induced proliferation, migration and invasion of the cells similar to that observed in asbestos-exposed cells. An up-regulation of several key genes known to be important in cell invasion, notably matrix metalloproteinase-2 (MMP-2), was observed in the exposed mesothelial cells as determined by real-time PCR. Western blot and enzyme activity assays confirmed the increased expression and activity of MMP-2. Whole genome expression microarray analysis further indicated the importance of MMP-2 in the invasion gene signaling network of the exposed cells. Knockdown of MMP-2 in CNT and asbestos-exposed cells by shRNA-mediated gene silencing effectively inhibited the aggressive phenotypes. This study provides new evidence for CNT-induced cell invasion and indicates the role of MMP-2 in the process.
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| Overall design |
Whole genome expression profiling was conducted on human immortalized pleural mesothelial cells (MeT5A) following 4 month in vitro sub-chronic exposure to six separate treatments to assess differences in carbon nanotube (CNT) vs. asbestos potential tumorigenesis signaling. Dispersed single wall CNT (D-SWCNT), multi-wall CNT (D-MWCNT), crocidolite asbestos (ASB) and saline (SAL) exposed cells were compared to Survanta® dispersant (DISP) passage control cells. DISP and SAL cells served as control treatments for CNT- and ASB-exposed cells, respectively. Each treatment possessed 3 biological cDNA replicates. One technical replicate was performed per biological sample.
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| Contributor(s) |
Stueckle TA, Rojanasakul LW |
| Citation(s) |
23924264 |
| Submission date |
Jul 14, 2013 |
| Last update date |
Nov 23, 2015 |
| Contact name |
Todd A Stueckle |
| E-mail(s) |
tstueckle@cdc.gov
|
| Phone |
304 285-6098
|
| Organization name |
National Institute for Occupational Safety and Health
|
| Department |
Health Effects Laboratory Division
|
| Lab |
Pathology and Physiology Research Branch
|
| Street address |
1095 Willowdale Road
|
| City |
Morgantown |
| State/province |
WV |
| ZIP/Postal code |
26505 |
| Country |
USA |
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| Platforms (1) |
| GPL10191 |
NimbleGen Homo sapiens HG18 090828 opt expr HX12 (12x135k) |
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| Samples (15)
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| GSM1185688 |
MeT5A_dispersant_4month_rep1 |
| GSM1185689 |
MeT5A_dispersant_4month_rep2 |
| GSM1185690 |
MeT5A_dispersant_4month_rep3 |
| GSM1185691 |
MeT5A_dispersed single wall carbon nanotube_4month_rep1 |
| GSM1185692 |
MeT5A_dispersed single wall carbon nanotube_4month_rep2 |
| GSM1185693 |
MeT5A_dispersed single wall carbon nanotube_4month_rep3 |
| GSM1185694 |
MeT5A_dispersed multiwall carbon nanotube_4month_rep1 |
| GSM1185695 |
MeT5A_dispersed multiwall carbon nanotube_4month_rep2 |
| GSM1185696 |
MeT5A_dispersed multiwall carbon nanotube_4month_rep3 |
| GSM1185697 |
MeT5A_crocidolite asbestos_4month_rep1 |
| GSM1185698 |
MeT5A_crocidolite asbestos_4month_rep2 |
| GSM1185699 |
MeT5A_crocidolite asbestos_4month_rep3 |
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| Relations |
| BioProject |
PRJNA212005 |
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